June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Lack of Raptor in the neural retina causes abnormalities in retinal vascular development, disorganization of retinal lamination and loss of visual acuity
Author Affiliations & Notes
  • Dejuan Kong
    Ophthalmology and Visual Science, University of Michgen, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Heather Hager
    Ophthalmology and Visual Science, University of Michgen, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Lynda Elghazi-Cras
    Ophthalmology and Visual Science, University of Michgen, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Xuwen Liu
    Ophthalmology and Visual Science, University of Michgen, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Patrice E Fort
    Ophthalmology and Visual Science, University of Michgen, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Thomas W Gardner
    Ophthalmology and Visual Science, University of Michgen, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Steven F Abcouwer
    Ophthalmology and Visual Science, University of Michgen, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Dejuan Kong, None; Heather Hager, None; Lynda Elghazi-Cras, None; Xuwen Liu, None; Patrice Fort, None; Thomas Gardner, None; Steven Abcouwer, None
  • Footnotes
    Support  R01EY020582, NIH P30 EY007003, Taubman Scholar Grant.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4054. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Dejuan Kong, Heather Hager, Lynda Elghazi-Cras, Xuwen Liu, Patrice E Fort, Thomas W Gardner, Steven F Abcouwer; Lack of Raptor in the neural retina causes abnormalities in retinal vascular development, disorganization of retinal lamination and loss of visual acuity. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4054.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : The mechanistic target of rapamycin (mTOR) kinase exists in two distinct complexes, mTORC1 and mTORC2, with only mTORC1 containing the regulatory-associated protein of mTOR (Raptor). mTORC1 is a key regulatory control point of metabolism and protein synthesis. Little is known about the role of mTORC1 in retinal physiology. To determine if mTORC1 is necessary for retinal development the effect of negating mTORC1 function in the embryonic neural retina on visual acuity and retinal anatomy was examined.

Methods : Six3cre mice were bred with Rptorf/f mice to cause conditional knockout (cKO) of Raptor expression in the neural retina beginning at approximately embryonic day 9. Six3cre-Rptorf/f mice were compared to Six3cre and to Rptorf/f controls. PCR confirmed Rptor gene editing and qRT-PCR confirmed a decrease of Raptor mRNA expression in whole retinas. Optokinetic response monitoring was used to examine visual acuity at 8 weeks of age. Optical coherence tomography (OCT) was used to examine retinal morphology and the presence of hyaloid vessels at 3 and 8 weeks of age. H&E staining of paraffin embedded retinal sections was used to examine retinal thickness and layer organization at 8 weeks of age. Calretinin immunofluorescence (IF) was used to examine lamination of the inner plexiform layer (IPL). Isolectin B4 (IB4) staining of flat-mounted retinas and hyaloid vasculaturefrom mice at postnatal day 12 (P12) was used to examine hyaloid vessel regression and retinal vessel development.

Results : Lack of mTORC1 resulted in a 90% deficit in mean visual acuity at 8 weeks of age compared to controls. OCT and H&E staining showed asymmetric thinness of the temporal retina and disorganization of retinal layers in 94% of Rptor cKO eyes. Calretinin IF demonstrated disorganization of amacrine cell processes strata in the inner plexiform layer (IPL). OCT also revealed the presence of persistent hyaloid vessels with associated retinal traction in Rptor cKO eyes at both 3 (100%) and 8 weeks (78%) of age. IB4 staining of P12 retinas revealed varying degrees (20-100%) of avascular area in Rptor cKO retinas, which was associated with degree of hyaloid vessel persistence.

Conclusions : Neural mTORC1 function is necessary for normal retinal development, hyaloid vessel regression, retinal vessel formation and visual acuity.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×